Health & Medical Anti Aging

Resveratrol -anti aging

What Is Resveratrol?

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a stilbenoid, a type of natural phenol, and aphytoalexin produced naturally by several plants when under attack by pathogens such asbacteria or fungi

The effects of resveratrol are currently a topic of numerous animal and human studies. Its effects on the lifespan of many model organisms remain controversial, with uncertain effects infruit flies,  and short-lived fish. In mouse and rat experiments, anticancer,anti-inflammatory, blood sugar-lowering and other beneficial cardiovascular effects of resveratrol have been reported. These results have yet to be replicated in humans.

In one positive human trial, extremely high doses (3–5 g) of resveratrol, in a proprietary formulation designed to enhance its bioavailability, significantly lowered blood sugar.  However, although it has been alluded to in review articles, the study itself has never been published in a peer-reviewed scientific publication. Despite the mainstream press alleging resveratrol's anti-aging effects, there are no accepted data to form a scientific basis for the application of these claims to mammals. At the present time, research on resveratrol is in its infancy and the long-term effects of supplementation in humans are not known.

Resveratrol is found in the skin of red grapes and in other fruits. However, red wine contains very little of it, in the order of one milligram per glass. Resveratrol has also been produced by chemical synthesis and by biotechnological synthesis (metabolic engineered microorganisms) and is sold as a nutritional supplement  derived primarily from Japanese knotweed.

images?q=tbn:ANd9GcT4N2My9tO29TtKxZSWxEl

            Resveratrol 

Resveratrol is a compound produced by many plant species and is thought to be helpful in reducing serum lipids and may have favorable cardiovascular implications. It is produced by Vitis Vinifera and Labrusca grapes and is found in grape products including red and white wines. Resveratrol has been proven effective in extending life up to 30% and is key in the prevention of many types of cancers and more over heart disease.

Resveratrol is studied by nutritionists and biochemists because of its potential as an anticancer and cardioprotective compound. Resveratrol belongs to the phytoalexin class of phytochemicals and functions as a moderate antioxidant, quenching free radical damage linked to several cancers. The compound has also demonstrated anti-inflammatory properties that help it to block reactions associated with the cancer process.

In humans, studies are underway to determine health benefits of Resveratrol in cancer and heart disease. Preliminary research results demonstrate that Resveratrol may have anti-infective, antioxidant, and anti-inflammatory properties. According to studies involving cancer-prone mice, Resveratrol seems to reduce the occurrence of skin tumors. Additional studies suggest that Resveratrol is unique because of its ability to battle cancer at all three steps of the cancer process: initiation, promotion, and progression.

Researchers believe that Resveratrol is partially responsible for the cholesterol-lowering effects of red wine. Epidemiologic and clinical studies suggest that high consumption of Resveratrol-rich foods may result in reduced cardiovascular disease risk, lowered total cholesterol, and lowered LDL cholesterol. Resveratrol's antioxidant properties may again be the mechanism at work in reducing the oxidation of LDL cholesterol. Currently scientists are exploring additional potential health benefits of Resveratrol.

It is a red wine extract that partially isolates the Resveratrol portion of the grapes containing the highest concentrations of Resveratrol like Muscadine. You would have to drink 20 glasses of red wine to achieve the same amount of Resveratrol available in one dose of it.

Historical sources:-

1).Resveratrol was first identified from the roots of the Japanese knotweed (ko-jo-kon in Japanese or Polygonum Capsidatum in Latin). Other plant sources include eucalyptus, spruce, pine, and lily, found naturally in: red wine, grapes, blueberries, peanuts, and various other plants.

2).It is also found in natural foods and in dietary supplements including:
red wine extracts, grape seed pills and extracts, & polygonum cuspidatum extracts among others. Resveratrol is found in most abundance, though, in the skin of grapes that are used to make red wine.The types of grapes used to make wine which contain resveratrol are Vitis vinifera, labrusca, and muscadine grapes. Compared to white wine, the fermentation period in the process of making red wine is longer. Thus red wine contains more resveratrol than white wine. This may explain the generally agreed-upon notion that drinking red wine in moderation has benefits to maintain a healthy heart. It is suggested that a moderate amount is an average of one to two drinks per day for men and one drink per day for women. In the case of wine, a drink is defined as 5 ounces or 148 ml. Since drinking too much alcohol increases the risk of problems such as alcoholism, high blood pressure, obesity, stroke, and breast cancer, it is recommended that people do not start drinking if they do not already drink alcohol.
                  
3).But in China, Resveratrol mainly is from the roots of polygonum cuspidate Rhizome.
Polygonum cuspidatum Siobet zucc as traditional Chinese medicine, is the Polygonaceae perennials of root and tuber polygonum cuspidatum, the plant is rich in resources, distributed in Sichuan, Shanxi and Hubei Province,. Resveratrol as a valid component, and the Glycoside-piceid (Polydatin) have anticancer, antioxidant, antiplatelet condensation, antibacterial, regulating lipid metabolism, protect cardiovascular system and the nervous system and other features. The literature reports, so far polygonum cuspidatum of resveratrol content in the most high, polygonum cuspidatum resveratrol has become the focus of the study.

Extraction process:-

A simple method for the quantitative extraction of resveratrol and its glycosides from grape berry skins has been developed. Optimal conditions for the extraction were investigated. Type of solvent, time, and temperature assayed influenced resveratrol and piceid yield. Adequate extraction was attained with ethanol/water (80:20 v/v) maintained at 60 °C for 30 min. Recovery (>96%) and reproducibility (6.83-15.13%) were satisfactory. After extraction, resveratrol and piceid isomers were quantified by high-performance liquid chromatography coupled to a ultraviolet-visible diode array detector. The amounts detected in 13 samples of 7 different varieties analyzed were, on average, 92.33 µg/g of dry skin for cis-piceid, 42.19 µg/g of dry skin for trans-piceid, and 24.06 µg/g of dry skin for trans-resveratrol. cis-Resveratrol was not detected in any sample. In grape berries infected by powdery mildew the contentw of these compounds were considerably increased and the degree of infection was positively related to their stilbene content.

Methods which be uesd to extract resveratrol from the Polygonum cuspidatum Siobet zucc include:

1) Enzyme Extraction:Cuspidatum except for containing resveratrol, also contains resveratrol glycosides,anthraquinone, stilbene, polysaccharides and amino acids, and other substances, in certain conditions Rresveratrol glycosides can turn into Resveratrol by taking off glucose groups under Enzymatic hydrolysis, Enzymatic hydrolysis can go by adding enzyme,or make use of  microorganism in plants. Enzymatic extraction from cuspidatum resveratrol has patent report. But this approach has disadvantages of low conversion rate , costing more, taking long , and so on.

2) Microwave Extraction:Research the impact of solvent type ,extraction time , temperature, microwave power, polygonum cuspidatum particle size and moisture and other major operating parameters on cuspidatum resveratrol yield, getting the best extraction condition : Methanol and acetone is the best extractant, temperature is 80?,time is 15 min, microwave power is 800 ~ 900W, polygonum cuspidatum particle size is 0.45 to 0.30 mm,  moisture content is 20%, resveratrol extraction rate is 0.55%.  

3) Ultrasonic Extraction:Treat cuspidatum as raw material, compared 5 ways of Resveratrol extraction effects of hot water extraction, backset, ultrasonic extraction, Soxhlet, magnetic agitator. extracting method of ultrasonic extraction is the best, and cost the shortest time.

4) Alkali dissolving and acid Precipitation Extraction :Because of Resveratrol containing less hydroxyl, its solubility in water is relatively low, under certain conditions, it can increase its solubility in the system by produceing the chemical reaction with some inorganic alkali and alkaline salt . By adjusting system pH, Resveratrol will precipitate out again,so Resveratrol can be extracted enrich by Alkali dissolving and acid precipitation . Compared to organic solvent extraction, it has features of easy process , safe and convenient operation, low cost, strong selection. 

5) CO2 supercritical Extraction: taking CO2 supercritical fluid to extract resveratrol in cuspidatum, which mainly applies a low polar substances extraction, pressure and temperature even has smaller selection.It has disadvantages that one-time investment is high in a production application on device, and maintenance cost is also high.
Conclusion:After extracting active components Resveratrol in cuspidatum , use HPLC to detect  content of Resveratrol. Through the comparison of five different extraction process, the trial results suggest: Ultrasonic extraction works best under a weak alkali ,with 10 times 80% ethanol the amount of pH = 8, extracts 4 times, and each 15min, Resveratrol extract's content up to 0.373%.

Resveratrol derivatives:- 

Resveratrol has been shown to possess antioxidant and anticancer activities, but little is known on the effect of resveratrol derivatives. Recently we have isolated resveratrol and its dimers and trimers from peony (Paeonia lactiflora) seeds, and reported their strong antioxidant and cytotoxic activity. In the present study, we have evaluated cellular effects of resveratrol derivatives; viniferin, gnetin H, and suffruticosol B on the proliferation and apoptosis in HL-60 cells in vitro. All resveratrol and its derivatives reduced viability of HL-60 cells in a dose-dependent manner with their IC(50) values of 20-90 microM. Ascending orders of IC(50) values were suffruticosol B, gnetin H, viniferin and resveratrol respectively. HL-60 cells treated with the four stilbenes exhibited the distinct morphological changes characteristics of cell apoptosis such as chromatin condensation, apoptotic bodies, and DNA fragmentations. A time-dependent histogram of the cellular DNA analyzed by flow cytometry revealed a rapid increase in subdiploid cells and a concomitant decrease in diploid cells exposed to 100 microM resveratrol for 0-24 h. Cells treated with 25 microM of resveratrol, viniferin, gnetin H, and suffruticosol B for 24 h resulted in increment of sub-G1 population by 51, 5, 11 and 59%, respectively. Treatment of cells with 0-20 microM resveratrol for 5 h produced a concentration-dependent decrease in cytochrome P450 (CYP) 1B1 mRNA levels. Suffruticosol B also suppressed CYP1B1 gene expression. These results demonstrated that resveratrol oligomers also strongly suppressed HL-60 cell proliferation, and induced DNA damage. In addition, CYP1B1 gene supression may suggest an involvement in the resveratrol-induced apoptosis in HL-60 cells.

Recent studies


Life extent:-

Sustaining the flickering hope that human aging might somehow be decelerated, researchers have found they can substantially extend the average life span of obese mice with a specially designed drug. The drug, SRT-1720, protects the mice from the usual diseases of obesity by reducing the amount of fat in the liver and increasing sensitivity to insulin. These and other positive health effects enable the obese mice to live 44 percent longer, on average, than obese mice that did not receive the drug, according to a team of researchers led by Rafael de Cabo, a gerontologist at the National Institute on Aging.

Drugs closely related to SRT-1720 are now undergoing clinical trials in humans.

The findings "demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals," Dr. de Cabo and colleagues write in Thursday's issue of the new journal Scientific Reports. Their conclusion supports claims that had been thrown in doubt by an earlier study that was critical of SRT-1720.

A drug that makes it cost-free to be obese may seem more a moral hazard than an incentive to good health. But the rationale behind the research is somewhat different: the researchers are trying to capture the benefits that allow mice on very low-calorie diets to live longer. It just so happens that such benefits are much easier to demonstrate in mice under physiological stress like obesity than in normal mice.

"The drugs could be used as a preventative to stave off diseases, but I don't think they will ever be an excuse to abuse your body," said David Sinclair, a biologist at HarvardMedicalSchooland co-chairman of the scientific advisory board of sritris, which developed SRT-1720.

The company, a small pharmaceutical concern in Cambridge, Mass., designed SRT-1720 and a set of similar drugs to mimic resveratrol — the trace ingredient of red wine that is thought to activate protective proteins called sirtuins.

The sirtuins help bring about the 30 percent extension of life span enjoyed by mice and rats that are kept on very low-calorie diets. Since few people can keep to such an unappetizing diet, researchers hoped that doses of resveratrol might secure a painless path to significantly greater health and longevity.

But large doses of resveratrol are required to show any effect, so chemical mimics like SRT-1720 were developed to activate sirtuin at much lower doses.

Sirtuins have proved to be highly interesting proteins, but the goal of extending life span was set back last year when extensive trials of resveratrol showed it did not prolong mice's lives, although it seemed to do them no harm. Another blow came in 2009, when biologists at Pfizer reported that SRT-1720 and other resveratrol mimics did not activate sirtuins and did not have any beneficial effects in fat mice.

The report by Dr. de Cabo and his colleagues may do much to rescue SRT-1720 from this shadow. They found that SRT-1720 offered substantial benefits to the fat mice, with no signs of toxicity. Unlike the Pfizer study, which was short term, they followed large groups of mice for over three years.

"This is good evidence that this compound has a positive effect on the physiology of the obese animal, and that is definitely promising for humans," said Jan Vijg, an expert on aging at the Albert Einstein College of Medicine in theBronx.

Dr. de Cabo and his team "make a reasonable case" that the compound works by activating sirtuins, although they have not proved it, Dr. Vijg said.

In one sense it does not much matter how the drug obtains its effects, as long as it works. But the credibility of SRT-1720 and its cousins also rests on their design as sirtuin activators.

Despite the positive new results with SRT-1720, Sirtris is not putting it into clinical trials because the company believes another of its resveratrol mimics, SRT-2104, is more promising. That drug "is more suitable for human consumption," said Dr. Sinclair, a co-author of Dr. de Cabo's report.

"Questions were raised about the molecules and if they are working the way we said they were," Dr. Sinclair said. "But with this paper, the weight of evidence is shifting back in favor of the premise that we can tweak the aging pathway with drugs."

Obese mice are a standard research tool, but experts differ as to how relevant they are to humans. "They've poisoned the mice with this high-fat diet that makes them very sick indeed, and with SRT-1720 they can reverse some portion of that illness," said Dr. Richard A. Miller, an expert on aging mice at the University of Michigan.

Dr. Miller said the finding "looks like something people should pay a lot of attention to," but added that the study would have been even more interesting if it had shown an effect on normal mice.

Dr. de Cabo and his team included normal, untreated lean mice in their study as a control group for the treated and untreated fat mice. The treated fat mice lived longer than the untreated ones, but died long before the normal mice. Although the treated fat mice lived significantly longer on average, there was little difference between their maximum life span and that of the untreated mice. The drug, in other words, helped the fat mice enjoy more of their available life span without increasing the span itself.

The researchers' findings would be more significant if they had showed that SRT-1720 prolonged the lives of normal mice. Dr. Sinclair said that this leg of the study had been started at the same time, but that the treated normal mice were taking longer to die and could not be reported with the others. Dr. de Cabo said the results were "encouraging" but could not be discussed until they were published early next year. But Dr. Vijg noted that since the drug did not extend the maximum life span of fat mice, it would be surprising if it did so with lean mice.

Some researchers say that too much attention has been given to resveratrol and its sirtuin-activating mimics, and that other compounds like the antibiotic rapamycin may be even more promising. But the sirtuins "are worth a lot of attention even though some of the early claims have proved hard to reproduce," Dr. Miller said.

Because of the uncertainty about several earlier findings, the sirtuin field has become polarized. "Some people are strongly in support, and others are convinced there's nothing there," said Brian Kennedy, president of the Buck Institute for Research on Aging. He described himself as standing in the middle, but hopeful that the sirtuins would turn out to be "key modulators of aging."

Anti-cancer:-

Resveratrol, a phytoalexin found in the skin of grapes, is believed to have multiple bioactivities including anti-cancer, anti-carcinogenesis and antiinflammatory. The mechanisms by which resveratrol might produce these effects are not well understood. In this study, malignant human pancreatic cancer cells were treated without or with resveratrol in combination with ionizing radiation (IR), and then the mitochondrial function of treated cells was evaluated using several standardized assays. They include the Calcein AM method for mitochondria transition pore; the JC-1 staining method for mitochondria membrane potential; the CM-H2DCFDA method for reactive oxygen species; and the Annexin V/propidium iodide (PI) method for apoptosis/cell death. Our results indicated that pore function was partially intact after resveratrol, but resveratrol probably interfered with the accumulation of intracellular Calcein AM;  depolarization of the mitochondria membrane was increased in the resveratrol treated cells, consistent with mitochondrial dysfunction; ROS was slightly increased with resveratrol, a phenomenon that was greatly increased when this agent was combined with IR; and  in parallel with the above changes in mitochondrial and drug transport, cells treated with resveratrol showed increased apoptosis as measured by Annexin V/PI staining. In summary, the anti-cancer effect of resveratrol is associated with the damage of mitochondrial function that leads to increased ROS, apoptosis, and possibly intracellular drug accumulation via inhibition of proteins involved in multi-drug resistance (MDR).

Other benifits:-

Red wine, in moderation, has long been thought of as heart healthy. The alcohol and certain substances in red wine called antioxidants may help prevent heart disease by increasing levels of "good" cholesterol and protecting against artery damage.

While the news about red wine might sound great if you enjoy a glass of red wine with your evening meal, doctors are wary of encouraging anyone to start drinking alcohol. That's because too much alcohol can have many harmful effects on your body.

Still, many doctors agree that something in red wine appears to help your heart. It's possible that antioxidants, such as flavonoids or a substance called resveratrol, have heart-healthy benefits.

Red wine seems to have even more heart-healthy benefits than other types of alcohol, but it's possible that red wine isn't any better than beer, white wine or liquor for heart health. There's still no clear evidence that red wine is better than other forms of alcohol when it comes to possible heart-healthy benefits.

Antioxidants in red wine called polyphenols may help protect the lining of blood vessels in your heart. A polyphenol called resveratrol is one substance in red wine that's gotten attention.

Resveratrol might be a key ingredient in red wine that helps prevent damage to blood vessels, reduces "bad" cholesterol and prevents blood clots.

Most research on resveratrol has been done on animals, not people. Research in mice given resveratrol suggests that the antioxidant might also help protect them from obesity and diabetes, both of which are strong risk factors for heart disease. However, those findings were reported only in mice, not in people. In addition, to get the same dose of resveratrol used in the mice studies, a person would have to drink over 60 liters of red wine every day.

Some research shows that resveratrol could be linked to a reduced risk of inflammation and blood clotting, both of which can lead to heart disease. More research is needed before it's known whether resveratrol was the cause for the reduced risk.

Side effect:-

Every supplement or medication that we take has its benefits and drawbacks.  Side effects are something to consider, no matter what substance you're taking.  Every supplement has potential side effects.  This is especially true with newer supplements- such as resveratrol- that haven't been extensively tested or studied in people.

Understand that not all side effects are undesirable.  Many previously introduced drugs have had positive (and unexpected) side effects.  For example, the well-known ED drug Viagra was originally intended to help men with heart disease.  It's now the most prescribed ED drug worldwide.   That example may be a bit off-color, but it reinforces the idea that side effects can be either an asset or a liability.

As far as resveratrol is concerned, most reports of side effects are anecdotal- that is, they are based more on personal accounts than on medical studies.  With this lack of research, determining the benefits and risks is pretty tricky.

If you decide to take this supplement, consider that you may or may not experience one or more of these potentially negative effects.
  • Stomach cramping/diarrhea:  occurs more frequently in resveratrol formulas that are lower-concentration (50% or less), or of poor quality. (Which is why it's very important to choose a high quality resveratrol supplement
  • Common: Decreased appetite (some may see that as a bad thing).
  • Infrequent: Some users report a jittery feeling (like a caffeine "buzz") soon after ingestion.
  • Infrequent: Tingling or numbness in the arms, hands, legs and feet. This may happen soon after you take the supplement, but is said to last only a few minutes, and usually subsides after a few days of taking resveratrol.
  • Rare: Skin Patches: Although rare, skin patches on legs are sometimes reported by people.
  • Very Rare: Joint pain/arthritis: Very rare, but this may start or increase with higher doses of resveratrol at 2 grams or more.
  • Very Rare: Tendinitis pain (mostly in the Achilles tendon, but has been reported elsewhere with high doses of 2 grams or more).

This list is by no means scientifically researched, but it's compiled through personal accounts of people who have had experience with resveratrol.  Tendinitis pain and numbness which occur at high doses of 2 grams or more in the extremities, seem to be the most common reported side effects, and both diminish over time.


Leave a reply